Sub-Saharan Africa has the highest burden of disease due to human immunodeficiency virus (HIV) with approximately 25 million HIV-infected persons, including 2.9 million children. Over 1.3 million HIV-infected women gave birth in 2013 and an estimated 210,000 children were newly infected with HIV. Strategies to prevent mother-to-child transmission have been effective in reducing the burden of pediatric HIV and led to endorsement of a global plan in 2011 to eliminate mother-to-child HIV transmission and reduce HIV-related mortality among HIV- infected women and children by 90%. Reducing pediatric HIV-related morbidity and mortality will require health systems with the capacity to diagnose HIV infection infants and promptly and effectively administer antiretroviral therapy. Early infant diagnosis remains challenging in sub- Saharan Africa, particularly in rural areas, due to the lack of affordable and accessible laboratory tests. A point-of-care test for early infant diagnosis that is valid, low-cost, and easily administered would greatly improve access to testing, linkage to care and retention, and earlier treatment initiation. The Northwestern Global Health Foundation has developed a point-of-care test and recently received a market-entry grant from UNITAID to scale-up production. This proposal will evaluate use of this test in rural southern Zambia, a priority country in the global plan to eliminate pediatric HIV and a setting where the test will be most widely used. The objectives of this proposal address priority areas outlined by the Office of AIDS Research for research in international settings, and include: 1) evaluating the feasibility of implementing the point-of-care p24 antigen test at 6 weeks and 6 months of age; 2) evaluating the performance of a novel point-of-care test at birth; and 3) evaluating outcomes and costs of different implementation strategies to determine how best to integrate new tests into current testing algorithms. Study outcomes will provide critical information on the feasibility and validit of this newly developed point-of-care test for early infant diagnosis in rural sub-Saharan Africa and how this test, as well as other similar point-of-care tests, should be incorporated into national HIV testing and treatment guidelines. Having a valid and affordable point-of-care test would change the landscape of early infant diagnosis in sub-Saharan Africa and significantly improve access to early treatment for HIV-infected infants.